It is a common problem for patients having undergone surgical procedures, especially surgery of the abdomen, to suffer from a particular bowel dysfunction called postoperative ileus (POI). “Ileus”, as used herein, refers to the obstruction of the bowel or gut, especially the colon. See, e.g., Dorland's Illustrated Medical Dictionary, p. 816, 27th ed. (W.B. Saunders Company, Philadelphia 1988). Ileus should be distinguished from constipation, which refers to infrequent or difficulty in evacuating the feces. See, e.g., Dorland's Illustrated Medical Dictionary, p. 375, 27th ed. (W.B. Saunders Company, Philadelphia 1988). Ileus may be diagnosed by the disruption of normal coordinated movements of the gut, resulting in failure of the propulsion of intestinal contents. See, e.g., Resnick, J., Am. J. of Gastroenterology 1997, 92, 751 and Resnick, J., Am. J. of Gastroenterology, 1997, 92, 934. In some instances, particularly following surgery, including surgery of the abdomen, the bowel dysfunction may become quite severe, lasting for more than a week and affecting more than one portion of the GI tract. This condition is often referred to as postoperative paralytic ileus and most frequently occurs after laparotomy (see Livingston, E. H. and Passaro, E. D. Jr., Digestive Diseases and Sciences 1990, 35, 121). Similarly, post-partum ileus is a common problem for women in the period following childbirth.
Currently, therapies for treating ileus include functional stimulation of the intestinal tract, stool softeners, laxatives, lubricants, intravenous hydration, nasogatric suction, prokinetic agents, early enteral feeding, nasogastric decompression, and the use of less invasive surgical procedures. These prior art methods suffer from drawbacks, for example, as lacking specificity for POI or post-partum ileus. And these prior art methods offer no means for prevention. If ileus could be prevented or more effectively treated, hospital stays, recovery times, and medical costs would be significantly decreased in addition to the benefit of minimizing patient discomfort. Adolor Corporation is presently in phase III clinical trials for a therapy to treat Postoperative ileus using Alvimopan (Entereg®). Adolor's therapy, however, utilizes opiod receptor antagonists, as opposed the present invention, which involves the use of PACAP and VIP receptor antagonists.